Context Increased bone fragility and reduced energy absorption to fracture associated with type 2 diabetes (T2D) cannot be explained by bone mineral density alone. This study, for the first time reports on alterations in bone tissue's material properties obtained from individuals with diabetes and known fragility fracture status. Objective To investigate the role of T2D in altering biomechanical, microstructural and compositional properties of bone in individuals with fragility fracture. Design Femoral head bone tissue specimens were collected from patients who underwent replacement surgery for fragility hip fracture. Trabecular bone quality parameters were compared in samples of two groups: non-diabetic (n=40) and diabetic (n=30), with a mean duration of disease 7.5±2.8 years. Results No significant difference was observed in aBMD between the groups. Bone volume fraction (BV/TV) was lower in the diabetic group due to fewer and thinner trabeculae. The apparent-level toughness and post-yield energy were lower in those with diabetes. Tissue-level (nanoindentation) modulus and hardness were lower in this group. Compositional differences in diabetic group included lower mineral:matrix, wider mineral crystals, and bone collagen modifications - higher total fAGEs, higher non-enzymatic-cross-link-ratio (NE-xLR), and altered secondary structure (Amide bands). There was a strong inverse correlation between NE-xLR and post-yield-strain, fAGEs and post-yield energy, and, fAGEs and toughness. Conclusion Current study is novel in examining bone tissue in T2D following first hip fragility fracture. Our findings provide evidence of hyperglycemia’s detrimental effects on trabecular bone quality at multiple scales leading to lower energy absorption and toughness-indicative of increased propensity to bone fragility.

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Febuxostat exhibits unprecedented solid forms with a total of 40 polymorphs and pseudopolymorphs reported. Polymorphs differ in molecular arrangement and conformation, intermolecular interactions, and various physicochemical properties, including mechanical properties. Febuxostat Form Q (FXT Q) and Form H1 (FXT H1) were investigated for crystal structure, nanomechanical parameters, and bulk deformation behavior. FXT Q showed greater compressibility, densification, and plastic deformation as compared to FXT H1 at a given compaction pressure. Lower mechanical hardness of FXT Q (0.214 GPa) as compared to FXT H1 (0.310 GPa) was found to be consistent with greater compressibility and lower mean yield pressure (38 MPa) of FXT Q. Superior compaction behavior of FXT Q was attributed to the presence of active slip systems in crystals which offered greater plastic deformation. By virtue of greater compressibility and densification, FXT Q showed higher tabletability over FXT H1. Significant correlation was found with anticipation that the preferred orientation of molecular planes into a crystal lattice translated nanomechanical parameters to a bulk compaction process. Moreover, prediction of compactibility of materials based on true density or molecular packing should be carefully evaluated, as slip-planes may cause deviation in the structure-property relationship. This study supported how molecular level crystal structure confers a bridge between particle level nanomechanical parameters and bulk level deformation behavior.

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